Journal article
Chemical synthesis of the (25 R)- and (25 S)-epimers of 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding glycine and taurine conjugates
Chemistry and physics of lipids, Vol.164(5), pp.368-377
2011
DOI: 10.1016/j.chemphyslip.2011.04.008
PMID: 21554864
Abstract
► The (25
R)- and (25
S)-epimers of unconjugated 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding
N-acylamidate conjugates with glycine or taurine were prepared starting from cholic acid in 14 steps. ► Each epimer of the three variants of unconjugated and conjugated C
27 5α-bile acids was efficiently separated by RP-HPLC and their structural characteristics, were revealed by the NMR. ► These C
27 5α-bile acids are likely key intermediates of bile acid biosynthesis from cholesterol.
The (25
R)- and (25
S)-epimers of C
27 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding
N-acylamidate conjugates with glycine or taurine were prepared starting from cholic acid in 14 steps. The principal reactions involved were (1) reduction of a key intermediary C
24
allo-cholic acid performate with NaBH
4/triethylamine/ethyl chloroformate, (2) iodination of the resulting 3,7,12-triformyloxy-5α-cholan-24-ol with I
2/triphenylphosphine; (3) nucleophilic substitution of the iodo derivative with diethylmethyl malonate/NaH; and (4) hydrolysis of the resulting 3,7,12-triformyloxy-25-methyl-26,27-diethyl ester with KOH, followed by decarboxylation of the geminal dicarboxylic acid with LiCl.
N-Acylamidation of the resulting (25
R)/(25
S)-3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid mixture with glycine or taurine afforded the corresponding epimeric mixtures of the glycine and taurine conjugates. The (25
R)- and (25
S)-epimers of the three variants of unconjugated and conjugated 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid were efficiently separated by HPLC on a reversed-phase C
18 column and their structural characteristics, particularly the chiral center at C-25, delineated using
1H and
13C NMR. These synthetic compounds should be useful as authentic reference standards for establishing their presence in bile as well as being useful in studies on the biosynthesis of
allo-bile acids from cholesterol.
Details
- Title: Subtitle
- Chemical synthesis of the (25 R)- and (25 S)-epimers of 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding glycine and taurine conjugates
- Creators
- Shoujiro Ogawa - Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, JapanKuniko Mitamura - Faculty of Pharmaceutical Sciences, Kinki University, Kowakae, Higashi-Osaka 577-8502, JapanShigeo Ikegawa - Faculty of Pharmaceutical Sciences, Kinki University, Kowakae, Higashi-Osaka 577-8502, JapanMatthew D Krasowski - Department of Pathology, University of Iowa Hospital and Clinics, Iowa City, IA 52242, USALee R Hagey - Department of Medicine, University of California-San Diego, MC 006, La Jolla, CA 92093, USAAlan F Hofmann - Department of Medicine, University of California-San Diego, MC 006, La Jolla, CA 92093, USATakashi Iida - Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajousui, Setagaya, Tokyo 156-8550, Japan
- Resource Type
- Journal article
- Publication Details
- Chemistry and physics of lipids, Vol.164(5), pp.368-377
- Publisher
- Elsevier Ireland Ltd
- DOI
- 10.1016/j.chemphyslip.2011.04.008
- PMID
- 21554864
- ISSN
- 0009-3084
- eISSN
- 1873-2941
- Language
- English
- Date published
- 2011
- Academic Unit
- Pathology
- Record Identifier
- 9984047716102771
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